1. Field of the Invention
The present invention relates to a pharmaceutical composition for preventing and treating cancer comprising C12orf59 protein or a fragment thereof, or a polynucleotide encoding the same as an active ingredient.
2. Description of the Related Art
C12orf59 (chromosome 12 open reading frame 59) gene has been well kept in human, chimpagne, dog, cow, mouse, rat, and chicken. Two isoforms of its nucleotide sequence have been reported (BC131523, 183a.a.; NM_153022, 163a.a.). This protein has been presumed as a membrane protein considering the amino acid sequence thereof, but the function of this protein has not been disclosed, yet.
In some patent descriptions (WO2010/037859 and US 2009/0163435), the involvement of C12orf59 gene in cancer has been proposed, which is though only in relation to the gene expression regulation by the treatment of anti-cancer drug. Up to date, the expression regulation and function of C12orf59 gene involved in cancer have not been explained, yet.
Cancer is one of the toughest diseases threatening human health most, which is developed by a series of cell mutation in which cells are proliferated unlimitedly and uncontrollably and hence immortalized.
A variety of biochemical mechanisms in relation to cancer have been disclosed and hence therapeutic agents have also been developed. However, any fundamental treatment method for cancer has not been established, yet. Studies have been actively undergoing to identify various biomolecules involved in cancer and thereby to develop a drug targeting such molecules, and attempts have also been made to increase cancer treatment effect by utilizing the combination of developed drugs. Therefore, it can be said that the task to identify a target molecule involved in cancer is very important.
Colorectal cancer is a kind of incurable diseases which causes million illnesses every year over the world, among which 530,000 patients are killed. This disease increases so fast as to take the third place (12.7%) of total cancer cases in Korea, which seems to be partly attributed to aging and the change in dietary pattern. The recently developed anticancer agents that are effective in treating colorectal cancer are exemplified by fluoropyrimidines such as 5-FU, UFT and capecitabine (product name: XELODA®); irinotecan (product name: CAMPTO®); and oxaliplatin. Seven largest pharmaceutical markets including those in USA and Europe for colorectal cancer treatment agents amount to $900 million today, which is expected to grow fast to $7,800 million in 2017. However, there are always disadvantages of continuous use of these drugs, which are resistance and side effects. Therefore, it is requested to study further to develop a novel treatment agent.
Carcinoembryonic antigen (CEA), which has been used as a marker for diagnosing colorectal cancer, is a kind of glycoproteins normally generated in the prebirth stage. The production of this protein is normally stopped before birth. If CEA level in adult is higher than that in a newborn baby, it presents the possibility of colorectal cancer or other cancers. However, the CEA level can be increased in liver cirrhosis, liver failure, and alcoholic pancreatitis patients and smokers as well. Therefore, the CEA level is used for diagnosing cancer supplementarily.
The present inventors have studied to develop a cancer diagnosis or cancer treatment agent, and as a result confirmed the expression of C12orf59 gene in cancer cell line. Particularly, when C12orf59 protein or a fragment thereof was over-expressed in cancer cell line, ITGA5 expression involved in cancer cell invasion was decreased, indicating the reduction of cancer cell invasion. When C12orf59 gene expression was suppressed in colorectal cancer cell line, cancer cell invasion was increased and cancer cell survivability was increased as well, leading to the activation of various cell signal transmission pathways. The above results indicate that C12orf59 gene has a function as a tumor suppressor. Additionally, the present invention confirmed that particular peptides originated from isoforms 1 and 2 of C12orf59 protein effectively inhibit invasion of cancer cells and metastasis. Therefore, the present inventors finally completed this invention by confirming that C12orf59 gene or protein can be effectively used for the pharmaceutical composition for preventing and treating cancer and for the method for screening cancer diagnosis or cancer treatment agent candidate substances. Additionally, the present invention was completed upon confirming that the particular peptides originated from isoforms 1 and 2 of C12orf59 proteins can be used in preventing and treating cancer.